Rapid eye movement (REM) latency and neuroendocrine responses to cholinergic agonist administration are enhanced in adults with major depression. With the use of cholinergic agonists and antagonists, we will delineate further the involvement of muscarinic cholinergic systems in both adult and adolescent depression. Our preliminary data with the muscarinic cholinergic antagonist scopolamine suggest that both adolescent and adult depressives respond comparably, but to a greater extent than normal age-matched controls. Further, our data support the view that REM sleep and hypothalamo-pituitary-adrenal (HPA) axis abnormalities represent "trait" and "state" phenomena, respectively. A greater understanding of the physiology and pathophysiology of muscarinic cholinergic systems in normal and depressives, as revealed by the responses of REM latency and the HPA axis to cholinergic challenges, will lead to findings that should help elucidate basic neurophysiologic mechanisms and have important clinical implications and applications to depression.